BOSTON -- Few patients develop antibodies to liraglutide (Victoza), and the drug's therapeutic effects aren't blunted in those who do, researchers said here.

Action Points

Explain to interested patients that antibodies to injected peptide drugs can diminish their efficacy, although this study indicated that such an effect did not occur with liraglutide.

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

BOSTON -- Few patients develop antibodies to liraglutide (Victoza), and the drug's therapeutic effects aren't blunted in those who do, researchers said here.

In a pooled analysis, only 8.6% of patients developed such antibodies, and their reductions in glycated hemoglobin (HbA1c) were the same as in those who didn't develop antibodies, according to Alan J. Garber, MD, PhD, of Baylor College of Medicine in Houston, and colleagues.

They reported their findings at a poster session during the American Association of Clinical Endocrinologists meeting here.

"This shows that patients don't develop a lot of antibodies, that it doesn't happen in that many people," Garber told MedPage Today. "And in the people who do have an antibody response, liraglutide's effects aren't blunted."

Garber said peptide drugs have the potential to induce antibodies, based on their similarity to the native peptide or protein.

Glucagon-like peptide-1 (GLP-1) agonists vary in their homology to human GLP-1. Liraglutide is 97% homologous, while another analogue, exenatide (Byetta), is 53% homologous.

"Any injected protein will create antibodies –- that's true if you inject insulin, and it's true if you inject liraglutide," he said. "Liraglutide is virtually identical to normal human GLP-1, but as soon as you inject a protein, you create a low-level antibody response."

Those antibodies can bind to the peptide drug and alter its pharmacokinetics, thereby decreasing efficacy.

For instance, the researchers said that about 50% of patients taking exenatide in phase III trials developed antibodies to it, with 3% to 6% having high antibody titers associated with decreased efficacy.

So to investigate whether liraglutide was similarly affected, the researchers conducted a pooled analysis of four phase III studies to assess the prevalence of anti-liraglutide antibodies. The studies each lasted six to 12 months.

All the samples that were positive for these antibodies were also tested for cross-reactivity to native GLP-1 and for a neutralizing effect on liraglutide in vitro. Changes in HbA1c were a measurement of clinical efficacy.

The researchers found that anti-liraglutide antibodies were present in 8.3% of patients treated with a 1.8-mg dose, 8.7% of those treated with a 1.2-mg dose, and 9.2% for those on a 0.6-mg dose.

Overall, 8.6% of the 1,185 patients in the analysis generated antibodies to liraglutide.

Among these antibody-positive patients, 11.8% had neutralizing antibodies, and 55% had antibodies that also reacted with native GLP-1.

Yet the presence of anti-liraglutide antibodies had no effect on the drug's efficacy. In the 1.8-mg arm, patients positive for antibodies had a mean HbA1c reduction of 1.1 percentage points, while those negative for antibodies had a 1.2-point reduction.

In the 1.2-mg group, antibody-positive patients had a mean HbA1c reduction of 1.3 percentage points compared with 1.2 points for antibody-negative patients.

And similarly, there was no difference in reduction in the 0.6-mg arm, whether patients were positive or negative for antibodies.

The researchers concluded that the immunogenic potential of liraglutide is low because of its high homology to native GLP-1.

Gerber noted that antibody-positive patients "may have some local skin effects." For instance, nine patients with liraglutide antibodies reported injection site reactions, although overall, no patients withdrew from any of the trials due to adverse events.

The study was supported by Novo Nordisk. Garber serves on the company's advisory board.

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